Infections with numerous viruses result in profound alterations in the immune system. The goals of this project have been to determine how retroviruses affect immune cell interactions and growth. Studies of mice infected with murine leukemia viruses (MuLV) that induce a severe immunodeficiency syndrome, MAIDS, demonstrated that IFN was required for normal progression of disease. To understand IFN signaling in greater depth, we have studied mice with a null mutation of ICSBP, a transcriptional factor of the IFN regulatory factor (IRF) family induced by IFN. These studies have demonstrated a prominent role for IRF family members in regulating normal and aberrant hemopoiesis. We are working on determining how this family of transcription factors influences the proliferation, differentiation and regulation of cell death in the myeloid and lymphoid lineages. An in depth understanding of hemopoiesis will permit more effective development of gene therapy strategies involving hemopoietic stem and progenitor cells. We have previously found that mice expressing high levels of ecotropic MuLV have a high incidence of B cell lymphomas of various histologic types that may prove informative for understanding lymphomas in humans. These tumors are being studied to determine the role of novel oncogenes affected by insertional mutagenesis on the development of B lineage tumors. Since oncogenes and tumor suppressors have normal cellular counterparts, these studies should provide new insights into B cell biology.